Pioglitazone improves obesity type diabetic nephropathy: relation to the mitigation of renal oxidative reaction.
Medications to treat hyperglycemia and hyperinsulinemia are expected to inhibit the accumulation of advanced glycation end-products in the diabetic kidney and improve renal function by inhibiting oxidative reactions. In this study, we examined the effect of pioglitazone, an insulin sensitizer, on diabetic nephropathy. Feed containing pioglitazone at 0.01 or 0.02% was given to Zucker-fatty rats for 27 weeks. Pioglitazone reduced plasma glucose, plasma insulin, and blood HbAlc levels. It also decreased plasma total cholesterol, triglyceride, phospholipid and cystatin C levels and inhibited the increase in urine of 8-hydroxydeoxyguanosine and in plasma of malondialdehyde. In the histopathological examinations, pioglitazone inhibited diffusive or nodular thickening of the mesangial matrix, atrophy of the proximal convoluted tubule, thickening of the basement membrane of the tubule, and mild cellular infiltration (mostly small lymphocytes) in the stroma. Furthermore, pioglitazone inhibited the mRNA expression of the receptor for advanced glycation end-products (RAGE) and that of transforming growth factor-beta. Long-term administration of pioglitazone improved hyperglycemia lipid profiles, hypercholesterolemia, and hyperinsulinemia and had a protective effect on diabetic nephropathy in Zucker-fatty rats.
Hirasawa
Yasushi
Y
Department of Pharmacobiology and Therapeutics, Faculty of Pharmacy, Meijo University, Gifu, Japan.
Matsui
Yukari
Y
Yamane
Kazusuke
K
Yabuki
Shin-Ya
SY
Kawasaki
Yukiko
Y
Toyoshi
Tohru
T
Kyuki
Kohei
K
Ito
Masanori
M
Sakai
Takayuki
T
Nagamatsu
Tadashi
T
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000032:analysis; D006147:Guanine / Q000031:analogs & derivatives / Q000652:urine; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008315:Malondialdehyde / Q000652:urine; D009765:Obesity / Q000150:complications*; D010084:Oxidation-Reduction / Q000187:drug effects; D010743:Phospholipids / Q000097:blood; D000077205:Pioglitazone; D051381:Rats; D011924:Rats, Zucker; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000032:analysis; D014280:Triglycerides / Q000097:blood
D000080242:8-Hydroxy-2'-Deoxyguanosine; D001786:Blood Glucose; D002784:Cholesterol; D055316:Cystatin C; D015891:Cystatins; D006442:Glycated Hemoglobin; D006147:Guanine; D007004:Hypoglycemic Agents; D007328:Insulin; D008315:Malondialdehyde; D010743:Phospholipids; D000077205:Pioglitazone; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D014280:Triglycerides; C525032:Cst3 protein, rat; C517652:hemoglobin A1c protein, human; C078307:8-oxo-7,8-dihydrodeoxyguanine